An in vivo high-resolution human brain atlas of synaptic density

Synapses are fundamental to the function of the central nervous system and are implicated in a number of brain disorders. Despite their pivotal role, a comprehensive imaging resource detailing the distribution of synapses in the human brain has been lacking until now. Here, we employ high-resolution PET neuroimaging in healthy humans (17F/16M) to create a 3D atlas of the synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A). Calibration to absolute density values (pmol/mL) was achieved by leveraging postmortem human brain autoradiography data. The atlas unveils distinctive cortical and subcortical gradients of synapse density that reflect functional topography and hierarchical order from core sensory to higher-order integrative areas - a distribution that diverges from SV2A mRNA patterns. Furthermore, we find a positive association between IQ and SV2A density in several higher-order cortical areas. This new resource will help advance our understanding of brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future neuroscience research. Significance statement Here, we present a high-resolution 3D in vivo brain atlas of synaptic density in the human brain. In the healthy human brain, distinctive cortical and subcortical gradients of synapse density reflect functional topography and hierarchical order from core sensory to higher-order integrative areas - a distribution that diverges from SV2A mRNA patterns. This brain atlas will help advance our understanding of human brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future research in clinical, translational and comparative neuroscience .